Is PRMT9 p.Asp258Val (c.773A>T) pathogenic?

PRMT9 p.Asp258Val (c.773A>T) is classified Conflicting classifications of pathogenicity in PRMT9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-08-02). AlphaMissense: likely pathogenic (0.9926); Ultra-rare (popmax 0.015%, amr); Associated with Neurodevelopmental abnormality.

What condition is associated with PRMT9 p.Asp258Val (c.773A>T)?

PRMT9 p.Asp258Val (c.773A>T) is associated with Neurodevelopmental abnormality (ClinVar).

How common is PRMT9 p.Asp258Val (c.773A>T) in the general population?

PRMT9 p.Asp258Val (c.773A>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about PRMT9 p.Asp258Val (c.773A>T)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

PRMT9 p.Asp258Val

c.773A>T · rs200956405 · VCV281602

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Neurodevelopmental abnormality

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic · top 1% in PRMT9
REVEL	0.721	pathogenic-leaning
SaProt	LLR -16.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.72	acceptor loss · deltas
Pangolin	Δ0.62	loss · gain 0.48 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 45 kb · p 0.019 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/60,004 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00112% 18/1,612,790 alleles · ultra-rare exomes 16/1,460,590 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.0032%	31,212
European (non-Finnish)	0.000594%	168,443

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRMT9
Protein: p.Asp258Val
Coding: c.773A>T
MANE Select: NM_138364
dbSNP: rs200956405
Type: single nucleotide variant
Location: chr4:147670714 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 4 PDB
Residue 258: the sam-dependent mtase prmt-type 1 domain

Full PRMT9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Neurodevelopmental abnormality — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRMT9 p.Gln382Lys Uncertain significance ★★ ⚠ same condition
PRMT9 c.576-2A>G Pathogenic ★ same condition
PRMT9 p.Arg359Ter Pathogenic ★ same condition
PRMT9 p.Gln440Ter Pathogenic ★ same condition
PRMT9 p.Glu139Ter Pathogenic ★ same condition
PRMT9 p.Gly189Arg Pathogenic ★ same condition
PRMT9 p.Leu86Ter Pathogenic ★ same condition
PRMT9 p.Trp73Ter Pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prmt9-p-asp258val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown